Precursors of praziquantel at Bayer and E. Merck

The discovery of praziquantel at Bayer and E. Merck is the latest chapter in a long series of attempts by these companies to develop drugs to combat schistosomiasis. Patients had a low tolerance toward the earliest drugs developed by Bayer and other firms, such as carbon tetrachloride, oil of chenopodium, sentonin, and pelletierine (Goth, 1976). Only in the late 1920s, when Bayer developed Fuadin (stibophen), was the firm able to offer a more broadly useful product against schistosomiasis. The drug had originally been developed for the veterinary market, and was then tested in an experiment by the Egyptian government on 150 patients (Verg et al., 1988). While it proved effective, Fuadin had to be injected in multiple doses, and thus was not appropriate for population-based schistosomiasis control programmes.

In 1953 Bayer introduced Miracil D (lucanthone hydrochloride), a thioxanthone, which used some of the knowledge gained in malaria research. This compound had been found effective against schistosomiasis (particularly against S.haematobium) in the Bayer laboratory in Elberfeld in 1943, but could not be tested overseas during the Second World War. After the war, once it had been tested in Egypt, the Congo, Southern Rhodesia, and Latin America, Miracil D was introduced in the market as a schistosomiside (Verg et al., 1988).

Other drugs, mostly manufactured by other firms, have been used in the treatment of schiostosomiasis in humans, including: antimonial compounds, such as antimony potassium tartarate or tartar emetic (effective against S. japonicum), sodium antimonyl gluconate, and stibocaptate; non-antimonials (also effective against S. japonicum), such as amoscanate (nithiocyaminum), and a combination of furapromidum and rectal dipterex; benzoimidazoles, such as niridazole (Ambilhar, which is effective against S. haematobium); and thioxanthones, such as hycanthone (Goth, 1970, 1976). The use of most of these drugs has now been discontinued, due to the availability of more effective and less toxic drugs, namely, praziquantel, oxamniquine, and metrifonate (Clark et al., 1988).

Along with their attempts to develop drugs for treatment in humans, both Bayer and E. Merck also tried to combat schistosomiasis by developing drugs to decrease the population of fresh water snails that act as intermediate hosts in the spread of schistosomiasis. One such drug, used effectively to control snail populations, was Bayluscide (niclosamide), developed by Bayer and first marketed in 1962. Bayer carried out successful trials in eight African countries, and a large field trial in 1967 in the Egyptian oasis El Fayoum, where 1.2 million people were living. This field trial was co-sponsored by the Egyptian and German governments (Verg et al., 1988).

While Bayluscide was successful in the field trial in reducing the snail population, and thus in decreasing the proportion of the population with schistosomiasis, several limitations of molluscicides became clear (Verg et al., 1988; WHO, 1993). The only places where the host snails could be efficiently and effectively contained with Bayluscide were geographically isolated areas like oases, that is, places where water was not flowing from a non-treated site to a treated site, and where the administration of the pesticide was in the hands of one local or national government. This realization led to an increased emphasis on research for drugs for treatment of humans, which culminated in the development of praziquantel, named Biltricide by Bayer.